The distortion-product otacoustic emission (DPOAE) at 2f1-f2 shows great potential as a powerful tool for the clinical diagnosis of sensorineural hearing losses. Previous studies of this emission in rabbits and rodents, by the PI and others, strongly support a "black-box" model in which the 2f1-f2 DPOAE is produced by two discrete cochlear sources, one dominant at high stimulus levels (above 60-70 dB SPL), and the other dominant at lower levels. However, the nature of the two sources, and their relationship to the hearing process, are obscure. A primary aim of the proposed project is to investigate the locations of, and the physiological mechanisms underlying, the two DPOAE sources, in guinea pigs, in order to gather the knowledge required to develop the PI's model, by incorporating known cochlear processes. Thus, suppression, interference, and localized noise-trauma paradigms will be used to test the hypothesis that the two DPOAE sources are located at different sites along the cochlear partition, relative to the primary-tone region. Additionally, DPOAEs and other otacoustic-emission types will be recorded concurrently with electrophysiological measures of cochlear function during manipulations thought to specifically impair the action of the cochlear amplifier. These experiments will enhance our understanding of the generation of DPOAEs and other emission phenomena and, specifically, will help to clarify the relationship[ of otacoustic emissions to the cochlear amplifier, thought to be based in outer hair-cell electromotility. Because of major differences of the properties of otacoustic emissions between small mammals and humans, it is not clear that the model of discrete low- and high-level DPOE sources, developed on the basis of data from small mammals, can be generalized to humans. A primary aim of the proposed project is to test the hypothesis that there are discrete low- and high-level DPOAE sources in human ears, by utilizing techniques, similar to those employed to identify the two DPOAE sources in small mammals, that specifically test predictions of the PI's model. These techniques include detailed measurement of DPOAE-amplitude and phase variations upon systematic changes of stimulus parameters and measurement of the effect of aspirin ingestion on DPOAEs elicited by low- and high- level stimuli. In addition, the relationship of DPOAEs and the other otacoustic-emission phenomena will be studied by concurrent measurement of DPOAEs and the other emission types, in guinea pigs during a variety of cochlear manipulations, and in humans during aspirin ingestion. These experiments will improve our understanding of the relationship of the various otacoustic-emission phenomena to each other, and to the hearing process. This knowledge will aid in the design, experimental testing, and interpretation of results of clinical tests utilizing otacoustic emissions.